Nano-therapeutic and/or -diagnostic delivery vehicles are typically macro- or supra-molecular multicomponent systems, ranging in size from 1-1,000 nm, that are either inherently therapeutic (e.g., no active pharmaceutical ingredient) or function as therapeutic or diagnostic delivery systems. To date, liposomal nanoparticles and biologics comprise a large proportion of the number of FDA-approved products or products in clinical trials used to treat and/or detect a variety of cancer types, while a number of polymer-based particle formulations are currently in early phase trials.
Desirable candidates for nanotherapeutic delivery systems share a common feature of incorporating and releasing a drug compound in a controlled manner, which can favorably alter drug bioavailability and pharmacokinetics, while minimizing off-target toxicities. Ideally, an imaging label is incorporated therein to assess their precise localization and retention at disease sites.
However, these systems function using different mechanisms. For example, antibody drug conjugates (ADCs) achieve lower drug toxicity primarily through active targeting of tumor cells and conditional release of drug molecules. Upon binding a cell surface antigen, active drug release occurs after cellular internalization and endosomal uptake. On the other hand, liposomes and polymer-based drug delivery systems, which are typically much larger assembled complexes (˜20-150 nm diameters) passively loaded with a greater payload (˜10,000 drug molecules for Doxil) or imaging agents, have generally lacked targeting capabilities (BIND-014 is an exception). Therefore, these complexes rely primarily on the well-known enhanced permeability and retention (EPR) effect for the successful delivery of nano-formulated drugs. While interstitial permeation of liposomes may be poor due to their size, the free drug is released through various mechanisms that are not entirely understood. For example, Abraxane (˜140 nm) relies on a different approach to enhance the bioavailability of a hydrophobic compound. In this case, a specific formulation of albumin and drug (paclitaxel) forms the initial complex, which is in turn estimated to disperse into smaller protein-drug aggregates upon injection.
Metastatic disease may effectively be treated with immunotherapies; however, a significant subpopulation will not respond due to lack of antigenic mutations or the immune-evasive properties of cancer. In addition, although radiation therapy (RT) is a standard treatment for cancer, local failures occur. Preclinical data indicate that RT can potentiate the systemic efficacy of immunotherapy, while activation of the innate and adaptive immune system can enhance the local efficacy of RT.
There remains a need for a platform that can be used for the detection, prevention, and/or treatment of cancer and other diseases.